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Abstract There is growing support and interest in postsecondary interdisciplinary environmental education, which integrates concepts and disciplines in addition to providing varied perspectives. There is a need to assess student learning in these programs as well as rigorous evaluation of educational practices, especially of complex synthesis concepts. This work tests a text classification machine learning model as a tool to assess student systems thinking capabilities using two questions anchored by the Food-Energy-Water (FEW) Nexus phenomena by answering two questions (1) Can machine learning models be used to identify instructor-determined important concepts in student responses? (2) What do college students know about the interconnections between food, energy, and water, and how have students assimilated systems thinking into their constructed responses about FEW? Reported here is a broad range of model performances across 26 text classification models associated with two different assessment items, with model accuracy ranging from 0.755 to 0.992. Expert-like responses were infrequent in our dataset compared to responses providing simpler, incomplete explanations of the systems presented in the question. For those students moving from describing individual effects to multiple effects, their reasoning about the mechanism behind the system indicates advanced systems thinking ability. Specifically, students exhibit higher expertise in explaining changing water usage than discussing trade-offs for such changing usage. This research represents one of the first attempts to assess the links between foundational, discipline-specific concepts and systems thinking ability. These text classification approaches to scoring student FEW Nexus Constructed Responses (CR) indicate how these approaches can be used, in addition to several future research priorities for interdisciplinary, practice-based education research. Development of further complex question items using machine learning would allow evaluation of the relationship between foundational concept understanding and integration of those concepts as well as a more nuanced understanding of student comprehension of complex interdisciplinary concepts.

Abstract Growth in the green jobs sector has increased demand for college graduates who are prepared to enter the workforce with interdisciplinary sustainability skills. Simultaneously, scholarly calls for interdisciplinary collaboration in the service of addressing the societal challenges of enhancing resilience and sustainability have also increased in recent years. However, developing, executing, and assessing interdisciplinary content and skills at the post-secondary level has been challenging. The objective of this paper is to offer the Food-Energy-Water (FEW) Nexus as a powerful way to achieve sustainability competencies and matriculate graduates who will be equipped to facilitate the transformation of the global society by meeting the targets set by the United Nations Sustainable Development Goals. The paper presents 10 curricular design examples that span multiple levels, including modules, courses, and programs. These modules enable clear evaluation and assessment of key sustainability competencies, helping to prepare graduates with well-defined skillsets who are equipped to address current and future workforce needs.

Abstract Human islets of Langerhans are composed mostly of glucagon-secreting α cells and insulin-secreting β cells closely intermingled one another. Current methods for identifying α and β cells involve either fixing islets and using immunostaining or disaggregating islets and employing flow cytometry for classifying α and β cells based on their size and autofluorescence. Neither approach, however, allows investigating the dynamic behavior of α and β cells in a living and intact islet. To tackle this issue, we present a machine-learning-based strategy for identification α and β cells in label-free infrared micrographs of living human islets without immunostaining. Intrinsic autofluorescence is stimulated by infrared light and collected both in intensity and lifetime in the visible range, dominated by NAD(P)H and lipofuscin signals. Descriptive parameters are derived from micrographs for ~ 103 cells. These parameters are used as input for a boosted decision-tree model (XGBoost) pre-trained with immunofluorescence-derived cell-type information. The model displays an optimized-metrics performance of 0.86 (i.e. area under a ROC curve), with an associated precision of 0.94 for the recognition of β cells and 0.75 for α cells. This tool promises to enable longitudinal studies on the dynamic behavior of individual cell types at single-cell resolution within the intact tissue.

Students pursue college degrees expecting to learn skills necessary to navigate adult life. While this is the expectation of most students, there is a lack of research examining the perceived effectiveness of real-world applicability in undergraduate degrees. Objective: The purpose of this phenomenological and constructivist study was to explore how college alumni perceive their educational experiences in terms of real-world preparedness. Methods: Eight participants in their mid-twenties (5 females, 3 males) were selected using purposeful sampling. Participants participated in informal, semi-structured, one-on-one Zoom interviews and demographic questionnaire responses. Results: Emerging themes indicated that alumni felt the relationships formed had a greater contribution to their life-readiness compared to their real-world curriculum. Other emerging themes revealed alumni believed they developed valuable skills through hands-on experience and group work. Recommendations were made by alumni for curriculum changes, including smaller class sizes and inclusion of more practical courses. Conclusions: Based on these findings, future research should aim to replicate this study using a broader range of alumni to further investigate this phenomenon, as well as studies that investigate various college types and student experiences.

Wildfires are an important source of carbonaceous aerosol in the atmosphere. Organic aerosol that absorbs light in the ultraviolet to visible spectral range is referred to as brown carbon (BrC), and its impact on Earth's radiative budget has not been well characterized. We collected water-soluble brown carbon using a particle-into-liquid sampler (PILS) on board a Twin Otter aircraft during the Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) campaign. Samples were collected downwind of wildfires in the western United States from August to September 2019. We applied size-exclusion chromatography (SEC) with ultraviolet-visible spectroscopy to characterize the molecular size distribution of BrC chromophores. The wildfire plumes had transport ages of 0 to 5 h, and the absorption was dominated by chromophores with molecular weights Da. With BrC normalized to a conserved biomass burning tracer, carbon monoxide, a consistent decrease in BrC absorption with plume age was not observed during FIREX-AQ. These findings are consistent with the variable trends in BrC absorption with plume age reported in recent studies. While BrC absorption trends were broadly consistent between the offline SEC analysis and the online PILS measurements, the absolute values of absorption and their spectral dependence differed. We investigate plausible explanations for the discrepancies observed between the online and offline analyses. This included solvent effects, pH, and sample storage. We suspect that sample storage impacted the absorption intensity of the offline measurements without impacting the molecular weight distribution of BrC chromophores.

Abstract Background Cardiac wasting is a detrimental consequence of cancer that has been traditionally ignored and often misinterpreted as an iatrogenic effect. Methods We conducted a retrospective study on 42 chemo‐naive patients affected by locally advanced head and neck cancer (HNC). Based on unintentional weight loss, patients were divided into cachectic and non‐cachectic. Left ventricular mass (LVM), LV wall thickness (LVWT), interventricular septal (IVS) thickness, left ventricular internal diameter diastolic (LVIDd), left ventricular internal diameter systolic (LVIDs), internal ventricular septum diastolic (IVSd), left ventricular posterior wall thickness diastolic (LVPWd) and LV ejection fraction (LVEF) were analysed by echocardiography. In parallel, we retrospectively analysed 28 cardiac autoptic specimens of patients who either died of cancer before chemotherapy or with a diagnosis of cancer at autopsy. Presence or absence of myocardial fibrosis at microscopic observation was used for sample stratification. Conventional histology was performed. Results Cachectic and non‐cachectic patients had a significantly different value of LVWT and IVS thickness and LVPWd. LVWT was 9.08 ± 1.57 versus 10.35 ± 1.41 mm (P = 0.011) in cachectic and non‐cachectic patients, IVS was 10.00 mm (8.50–11.00) versus 11.00 mm (10.00–12.00) (P = 0.035), and LVPWd was 9.0 (8.5–10.0) and 10.00 mm (9.5–11.0) (P = 0.019) in cachectic and non‐cachectic patients. LVM adjusted for body surface area or height squared did not differ between the two populations. Similarly, LVEF did not show any significant decline. At multivariate logistic regression analysis for some independent predictors of weight loss, only LVWT maintained significant difference between cachectic and non‐cachectic patients (P = 0.035, OR = 0.240; P = 0.019). The secondary analysis on autoptic specimens showed no significant change in heart weight, whereas LVWT declined from 9.50 (7.25–11.00) to 7.50 mm (6.00–9.00) in cardiac specimens with myocardial fibrosis (P = 0.043). These data were confirmed in multivariate logistic regression analysis (P = 0.041, OR = 0.502). Histopathological analysis confirmed severe atrophy of cardiomyocytes, fibrosis and oedema as compared with controls. Conclusions Subtle changes in heart structure and function occur early in HNC patients. These can be detected with routine echocardiography and may help to select appropriate cancer treatment regimens for these patients. Histopathological analysis provided conclusive evidence that atrophy of cardiomyocytes, oedema and fibrosis occur during cancer progression and may precede the onset of overt cardiac pathology. To our knowledge, this is the first clinical study that establishes a direct relationship between tumour progression and cardiac remodelling in HNCs and the first pathological study conducted on human cardiac autopsies from selected chemo‐naïve cancer patients.

In Italy, breast cancer is the most frequently diagnosed cancer in women, with 55,900 new cases in 2023 (over 90% in the early stages). Due to the screening, early diagnosis and adjuvant treatment, these patients have a 5-years survival rate of 87% after the diagnosis. There are 834,154 women in Italy with a previous diagnosis of breast cancer: most of these women require a follow-up. The AIOM, ESMO and ASCO Guidelines recommend for early breast cancer (EBC) a clinical follow-up with only physical examination (and eliciting of symptoms) and an annual X-ray mammography, on the basis of the results of two randomized trials published in 1994 that showed no benefit in overall survival with intensive follow-up. However, an Italian survey reported the application by 80% of oncologists of an intensive follow-up based on the individual patient’s risk of recurrence. In fact, the oncologists believe that an early diagnosis of locoregional or distant recurrence may allow an early start of very effective therapies. In this lack of up-to-date scientific data, many questions about follow-up remain unanswered and the few ongoing studies will provide results in several years. Non-compliance with guideline recommendations leads to increased costs for the healthcare system. Furthermore, management varies widely from centre to centre with regard to guideline recommendations, resulting in inequalities between patients. For these reasons, the follow-up of breast cancer should be reconsidered. In the absence of recent scientific evidence, a multidisciplinary group of breast cancer experts has initiated a Consensus on the follow-up of EBC according to the mini-Delphi methodology. The project will be completed by the end of 2024.

A combination of live imaging and immunofluorescence on donor islet cells uncover an anti-correlation of enzyme-bound NAD(P)H and insulin secretion power.

We present the characterization of a highly segmented “large area” hybrid pixel detector (Timepix3, 512 × 512 pixels, pixel pitch 55 µm) for application in space experiments. We demonstrate that the nominal power consumption of 6 W can be reduced by changing the settings of the Timepix3 analog front-end and reducing the matrix clock frequency (from the nominal 40 MHz to 5 MHz) to 2 W (in the best case). We then present a comprehensive study of the impact of these changes on the particle tracking performance, the energy resolution and time stamping precision by utilizing data measured at the Super-Proton-Synchrotron (SPS) at CERN and at the Danish Center for Particle Therapy (DCPT). While the impact of the slower sampling frequency on energy measurement can be mitigated by prolongation of the falling edge of the analog signal, we find a reduction of the time resolution from 1.8 ns (in standard settings) to 5.6 ns (in analog low-power), which is further reduced utilizing a lower sampling clock (e.g., 5 MHz, in digital low-power operation) to 73.5 ns. We have studied the temperature dependence of the energy measurement for ambient temperatures between −20 °C and 50 °C separately for the different settings.

Peripheral immune-checkpoint blockade with mAbs to programmed cell death receptor-1 (PD-1) (either nivolumab or pembrolizumab) or PD-Ligand-1 (PD-L1) (atezolizumab, durvalumab, or avelumab) alone or in combination with doublet chemotherapy represents an expanding treatment strategy for metastatic non-small cell lung cancer (mNSCLC) patients. This strategy lays on the capability of these mAbs to rescue tumor-specific cytotoxic T lymphocytes (CTLs) inactivated throughout PD-1 binding to PD-L1/2 in the tumor sites. This inhibitory interactive pathway is a physiological mechanism of prevention against dangerous overreactions and autoimmunity in case of prolonged and/or repeated CTL response to the same antigen peptides. Therefore, we have carried out a retrospective bioinformatics analysis by single-cell flow cytometry to evaluate if PD-1/PD-L1-blocking mAbs modulate the expression of specific peripheral immune cell subsets, potentially correlated with autoimmunity triggering in 28 mNSCLC patients. We recorded a treatment-related decline in CD4+ T-cell and B-cell subsets and in the neutrophil-to-lymphocyte ratio coupled with an increase in natural killer T (NKT), CD8+PD1+ T cells, and eosinophils. Treatment-related increase in autoantibodies [mainly antinuclear antibodies (ANAs) and extractable nuclear antigen (ENA) antibodies] as well as the frequency of immune-related adverse events were associated with the deregulation of specific immune subpopulations (e.g., NKT cells). Correlative biological/clinical studies with deep immune monitoring are badly needed for a better characterization of the effects produced by PD-1/PD-L1 immune-checkpoint blockade.

This paper presents the Swiss guideline for genetic counselling and testing of individuals with an increased probability for carrying mutations in high risk cancer predisposition genes, particularly BRCA1 and BRCA2. It aims to help providers of genetic counselling to identify valuable candidates for testing and serves as a basis for reimbursement claims to Swiss insurance companies.

Purpose In 2012, US Marines and Sailors began annual deployments to Australia to participate in joint training exercises with the Australian Defence Force and other partners in the region. During their training, US service members are exposed to a variety of infectious disease threats not normally encountered by American citizens. This paper describes a cohort of US Marines and Sailors enrolled during five rotations to Australia between 2016 and 2020.Participants Study participation is strictly voluntary. Group informational sessions are held prior to deployment to describe the study structure and goals, as well as the infectious disease threats that participants may encounter while in Australia. All participants provided written informed consent. Consented participants complete a pre-deployment questionnaire to collect data including basic demographic information, military occupational specialty, travel history, family history, basic health status and personal habits such as alcohol consumption. Blood is collected for serum, plasma and peripheral blood mononuclear cells (PBMC) processing. Data and specimen collection is repeated up to three times: before, during and after deployment.Findings to date From the five rotations that comprised the 2016–2020 Marine Rotational Force-Darwin, we enrolled 1289 volunteers. Enrolments during this period were overwhelmingly white male under the age of 24 years. Most of the enrollees were junior enlisted and non-commissioned officers, with a smaller number of staff non-commissioned officers and commissioned officers, and minimal warrant officers. Over half of the enrollees had occupational specialty designations for infantry.Future plans In the future, we will screen samples for serological evidence of infection with Burkholderia pseudomallei, Coxiella burnetii, Ross River virus, SARS-CoV-2 and other operationally relevant pathogens endemic in Australia. Antigenic stimulation assays will be performed on PBMCs collected from seropositive individuals to characterise the immune response to these infections in this healthy American population.

A space-based detector dedicated to measurements of γ-rays and charged particles has to achieve a balance between different instrumental requirements. A good angular resolution is necessary for the γ-rays, whereas an excellent geometric factor is needed for the charged particles. The tracking reference technique of γ-ray physics is based on a pair-conversion telescope made of passive material (e.g., tungsten) coupled with sensitive layers (e.g., silicon microstrip). However, this kind of detector has a limited acceptance because of the large lever arm between the active layers, needed to improve the track reconstruction capability. Moreover, the passive material can induce fragmentation of nuclei, thus worsening charge reconstruction performances. The Tracker-In-Calorimeter (TIC) project aims to solve all these drawbacks. In the TIC proposal, the silicon sensors are moved inside a highly-segmented isotropic calorimeter with a couple of external scintillators dedicated to charge reconstruction. In principle, this configuration has a good geometrical factor, and the angle of the γ-rays can be precisely reconstructed from the lateral profile of the electromagnetic shower sampled, at different depths in the calorimeter, by silicon strips. The effectiveness of this approach has been studied with Monte Carlo simulations and validated with beam test data of a small prototype.

Background: Melanoma is a serious skin cancer that has been on the rise in the United States. Some genetic component is apparent. Purpose: The purpose of this study was to identify demographic, clinical, attitudinal, and health belief factors associated with intention to obtain genetic testing for hereditary melanoma among unaffected first-degree relatives of melanoma patients at low to moderate risk for hereditary melanoma. Methods: Using contact information provided by index cases diagnosed with melanoma, 92 unaffected first-degree relatives were asked to complete questionnaires via mail. Results: The average age of respondents was 45.7 (plus or minus 12.8) years, and the majority were female (59%), currently married (80%), and Caucasian (98%). Only 11% of the sample was aware of genetic testing for hereditary melanoma prior to the survey. However, once such a test was described, 48% said they would take the test in the next six months if it were made available to them. Logistic regression analyses revealed that being married, physician recommendation, and helping family members make health care decisions were associated with intention to obtain genetic testing. Discussion: In light of these results, health education efforts for low-to-moderate-risk patients should include information about the clinical utility of genetic testing and the implications of test results for family members. Translation to Health Education Practice: As genetic testing for cancer becomes more widely available, demand for information will increase as well. Health educators will be instrumental in meeting the increased demand for such information and ensuring that those at low risk are appropriately informed and reassured. (Contains 3 tables.)

ABSTRACT Associations between leguminous plants and symbiotic nitrogen-fixing rhizobia are a classic example of mutualism between a eukaryotic host and a specific group of prokaryotic microbes. Although this symbiosis is in part species specific, different rhizobial strains may colonize the same nodule. Some rhizobial strains are commonly known as better competitors than others, but detailed analyses that aim to predict rhizobial competitive abilities based on genomes are still scarce. Here, we performed a bacterial genome-wide association (GWAS) analysis to define the genomic determinants related to the competitive capabilities in the model rhizobial species Sinorhizobium meliloti. For this, 13 tester strains were green fluorescent protein (GFP) tagged and assayed versus 3 red fluorescent protein (RFP)-tagged reference competitor strains (Rm1021, AK83, and BL225C) in a Medicago sativa nodule occupancy test. Competition data and strain genomic sequences were employed to build a model for GWAS based on k-mers. Among the k-mers with the highest scores, 51 k-mers mapped on the genomes of four strains showing the highest competition phenotypes (>60% single strain nodule occupancy; GR4, KH35c, KH46, and SM11) versus BL225C. These k-mers were mainly located on the symbiosis-related megaplasmid pSymA, specifically on genes coding for transporters, proteins involved in the biosynthesis of cofactors, and proteins related to metabolism (e.g., fatty acids). The same analysis was performed considering the sum of single and mixed nodules obtained in the competition assays versus BL225C, retrieving k-mers mapped on the genes previously found and on vir genes. Therefore, the competition abilities seem to be linked to multiple genetic determinants and comprise several cellular components. IMPORTANCE Decoding the competitive pattern that occurs in the rhizosphere is challenging in the study of bacterial social interaction strategies. To date, the single-gene approach has mainly been used to uncover the bases of nodulation, but there is still a knowledge gap regarding the main features that a priori characterize rhizobial strains able to outcompete indigenous rhizobia. Therefore, tracking down which traits make different rhizobial strains able to win the competition for plant infection over other indigenous rhizobia will improve the strain selection process and, consequently, plant yield in sustainable agricultural production systems. We proved that a k-mer-based GWAS approach can efficiently identify the competition determinants of a panel of strains previously analyzed for their plant tissue occupancy using double fluorescent labeling. The reported strategy will be useful for detailed studies on the genomic aspects of the evolution of bacterial symbiosis and for an extensive evaluation of rhizobial inoculants.

Here we provide demonstration that fast fluorescence fluctuation spectroscopy is a fast and robust approach to extract information on the dynamics of molecules enclosed within subcellular nanostructures (e.g., organelles or vesicles) which are also moving in the complex cellular environment. In more detail, Raster Image Correlation Spectroscopy (RICS) performed at fast timescales (i.e., microseconds) reveals the fast motion of fluorescently labeled molecules within two exemplary dynamic subcellular nanostructures of biomedical interest, the lysosome and the insulin secretory granule (ISG). The measurement of molecular diffusion is then used to extract information on the average properties of subcellular nanostructures, such as macromolecular crowding or molecular aggregation. Concerning the lysosome, fast RICS on a fluorescent tracer allowed us to quantitatively assess the increase in organelle viscosity in the pathological condition of Krabbe disease. In the case of ISGs, fast RICS on two ISG-specific secreting peptides unveiled their differential aggregation propensity depending on intragranular concentration. Finally, a combination of fast RICS and feedback-based 3D orbital tracking was used to subtract the slow movement of subcellular nanostructures from the fast diffusion of molecules contained within them and independently validate the results. Results presented here not only demonstrate the acquired ability to address the dynamic behavior of molecules in moving, nanoscopic reference systems, but prove the relevance of this approach to advance our knowledge on cell function at the subcellular scale.

A new generation magnetic spectrometer in space will open the opportunity to investigate the frontiers in direct high-energy cosmic ray measurements and to precisely measure the amount of the rare antimatter component in cosmic rays beyond the reach of current missions. We propose the concept for an Antimatter Large Acceptance Detector In Orbit (ALADInO), designed to take over the legacy of direct measurements of cosmic rays in space performed by PAMELA and AMS-02. ALADInO features technological solutions conceived to overcome the current limitations of magnetic spectrometers in space with a layout that provides an acceptance larger than 10 m2 sr. A superconducting magnet coupled to precision tracking and time-of-flight systems can provide the required matter–antimatter separation capabilities and rigidity measurement resolution with a Maximum Detectable Rigidity better than 20 TV. The inner 3D-imaging deep calorimeter, designed to maximize the isotropic acceptance of particles, allows for the measurement of cosmic rays up to PeV energies with accurate energy resolution to precisely measure features in the cosmic ray spectra. The operations of ALADInO in the Sun–Earth L2 Lagrangian point for at least 5 years would enable unique revolutionary observations with groundbreaking discovery potentials in the field of astroparticle physics by precision measurements of electrons, positrons, and antiprotons up to 10 TeV and of nuclear cosmic rays up to PeV energies, and by the possible unambiguous detection and measurement of low-energy antideuteron and antihelium components in cosmic rays.

This study aimed to determine if dietary modifications using a nutritional regimen could prevent or reduce the incidence of cancer therapy-induced diarrhea in patients with metastatic colorectal cancer and to evaluate the relationship of Vitamin D blood levels with diarrhea severity. Patients with metastatic colorectal cancer were enrolled. A Mediterranean diet, containing some special limitations aiming to reduce the risk of diarrhea, was administered before and during the entire chemotherapy program. Enrolled patients numbering 60/137 (44%) had diarrhea during chemotherapy. Adherence to the diet was high in 36 (26.3%) patients, medium in 94 (68.6%), and low in 7 (5.1%). Mean adherence to the diet was significantly lower in patients who experienced diarrhea with maximum grade 2–3 compared to those who had no diarrhea or grade 1 diarrhea (score = 5.4 ± 1.9 vs. 7.1 ± 1.5, p < 0.001). Patients with higher adherence to the diet had a lower risk of grade 2–3 diarrhea (odds ratio: 0.5 (95% CI: 0.3–0.7, p < 0.001)). In addition, patients who completed a higher number of chemotherapy cycles had an increased risk of grade 2–3 diarrhea (odds ratio: 1.2 (95% CI: 1.0–1.5, p = 0.02)). Of note, a lower level of Vitamin D correlated with an increased risk of G2-G3 diarrhea (p = 0.03). A diet based on vegetables with a controlled fiber content, Mediterranean Modified Healthy Diet (MMHD), is useful to control the incidence of cancer therapy-induced diarrhea.

In the last decade, cardiologists and oncologists have provided clinical and experimental evidence that cancer, and not only chemotherapeutic agents, can cause detrimental effects on heart structure and function, a consequence that has serious clinical implications for patient management. In parallel, the intriguing idea that heart failure (HF) may be an oncogenic condition has also received growing attention. A number of epidemiological and clinical studies have reported that patients with HF have a higher risk of developing cancer. Chronic low-grade systemic inflammation has been proposed as a major pathophysiological process linking the failing heart to the multi-step process of carcinogenesis. According to this view, pro-inflammatory mediators secreted by the damaged heart generate a favorable milieu that promotes tumor development and accelerates malignant transformation. HF-associated inflammation synergizes with tumor-associated inflammation, so that over time it is no longer possible to distinguish the effects of one or the other. Experimental studies have just begun to search for the molecular effectors of this process, with the ultimate goal that of identifying mechanisms suitable for anti-cancer target therapy to reduce the risk of incident cancer in patients already affected by HF. In this review we critically discuss strengths and limitations of clinical and experimental studies that support a causal relationship between HF and cancer, and focus on HF-associated inflammation, cardiokines and their endocrine functions linking one and the other disease.

An immune checkpoint blockade with mAbs to PD-1 and PD-L1 is an expanding therapeutic option for mNSCLC patients. This treatment strategy is based on the use of mAbs able to restore the anti-tumor activity of intratumoral T cells inhibited by PD-1 binding to PD-L1/2 on tumor and inflammatory cells. It has been speculated that a chronic status of systemic inflammation as well as the immunosenescence physiologically occurring in elderly patients may affect the efficacy of the treatment and the occurrence of irAEs. We performed a multi-institutional retrospective study aimed at evaluating the effects of these mAbs (nivolumab or atezolizumab) in 117 mNSCLC patients younger (90 cases) and older (27 cases) than 75 years in correlation with multiple inflammatory parameters (NLR, CRP, ESR, LDH and PCT). No differences were observed when the cohorts were compared in terms of the frequency of PFS, OS, inflammatory markers and immune-related adverse events (irAEs). Similarly, the occurrence of irAEs was strictly correlated with a prolonged OS survival in both groups. On the contrary, a negative correlation between the high baseline levels of inflammatory markers and OS could be demonstrated in the younger cohort only. Overall, PD-1/PD-L1-blocking mAbs were equally effective in young and elderly mNSCLC patients; however, the detrimental influence of a systemic inflammation at the baseline was only observed in young patients, suggesting different aging-related inflammation immunoregulative effects.

Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up.Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled in the GOLFIG-2 phase III trial) and 117 as second/third line (49 enrolled in the GOLFIG-1 phase II trial and 68 as compassionate use). One hundred twelve patients showed a primary left side and 67 a primary right side; K/N-ras mutational status was available in 74 cases, and an activating mutation was detected in 33. Kaplan–Meier and Cox regression analyses were carried out to relate PFS and OS with different parameters.Results: Overall, we recorded a mean PFS and OS of 15.28 (95% CI: 10.36–20.20) and 24.6 (95% CI: 19.07–30.14) months, respectively, with 14 patients surviving free of progression for 10 years. This regimen, in our updated survey of the GOLFIG-2 trial, confirmed superiority over FOLFOX in terms of PFS (hazard ratio (HR) = 0.58, p = 0.006) with a trend to a longer OS (HR = 0.69, P = 0.06) in the first line. Our analysis also confirmed significant antitumor activity in pre-treated patients, reporting a mean PFS and OS of 12.55 (95% CI: 7.19–17.9) and 20.28 (95% CI: 14.4–26.13) months, respectively. Immune-related adverse events (irAEs) were recorded in 24% of the cases and were related to a longer survival (HR = 0.36; P = 0.0001). Finally, patients' outcome was not correlated to sex, sidedness, and MT-K/N-ras.Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.

BACKGROUND Since the advent of high-throughput sequencing technologies, organised germline screening, independent of the personal and family cancer history, has been frequently proposed. Since ethnic and geographic populations significantly differ in their mutation spectra and prevalence, one critical prerequisite would be the knowledge of the expected carrier frequencies. OBJECTIVE For the first time, in a retrospective non-cancer related cohort from a single Swiss genetic centre, we systematically assessed the prevalence of secondary findings in 19 genes (BRCA1/2 plus 17 non-BRCA genes) previously designated by the US National Comprehensive Cancer Network (NCCN) for hereditary breast and ovarian cancer (HBOC) germline testing. DESIGN A total of 400 individuals without a cancer diagnosis undergoing whole-exome sequencing (WES) analysis for neurodevelopmental disorders (NDDs) from 2015 to 2017 at IMG Zurich were included after quality assessment. Among these, 180 were unaffected parental couples, 27 unaffected parental singles and 13 NDD index patients (mean age 43 years). The majority of the cohort was of Caucasian ethnicity (n = 336, 84.0%) and of Northwest European ancestry (n = 202, 50.5%), for 70 of whom (42.5%) an autochthonous Swiss descent was assumed. For WES filtering of rare, potentially actionable secondary variants in HBOC genes, an overall minor allele frequency (MAF) below 0.65% was used as cut-off. Each rare variant was manually evaluated according to the recommended ACGM-AMP standards, with some adaptations including “hypomorphic” as an additional distinct pathogenicity class. RESULTS Overall, 526 rare secondary variants (339 different variants) were encountered, with the BRCA1/2 genes accounting for 27.2% of the total variant yield. If stratified for variant pathogenicity, for BRCA1/2, three pathogenic variants were found in three females of Italian ancestry (carrier frequency of 0.8%). In the non-BRCA genes, five carriers of (likely) pathogenic variants (1.3%) were identified, with two Swiss individuals harbouring the same CHEK2 Arg160Gly variant known to be recurrent among Caucasians. Hence, the overall carrier rate added up to 2.0%. Additionally, seven various hypomorphic HBOC predisposing alleles were detected in 22 individuals (5.5%). CONCLUSION We provide the first evidence of a high prevalence of HBOC-related cancer susceptibility in the heterogeneous Swiss general population and relevant subpopulations, particularly in individuals of Italian descent. These pioneering data may substantiate population-based HBOC screening in Switzerland.

The quality of coffee is linked to the aroma created by the chemical reactions that occur during the roasting process. While it is generally thought that roasted coffee is a stable product with a relatively long shelf-life, little information is available on the evolution (kinetic) of the volatile organic compounds (VOCs) in the days immediately following the process. The aim of this study is to determine the evolution of VOCs released by coffee beans, on samples of Coffea arabica (three different origins) and Coffea canephora (1 single origin), by using a Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS) 24 hours after roasting, and for the next 9 days. Results confirmed the differences already highlighted in previous studies between the VOCs spectra of the two species. There were also significant differences in the intensity of emissions for the different origins of Coffea arabica, with the highest VOCs amount over time always detected in the Honduras Arabica samples. The involved detected protonated ions were grouped into three classes: compounds (ppbv) present with decreasing quantity ; weakly increasing; almost constant trend; or always increasing. A complex dynamic emerged for the different protonated ions over time, which not only affects the mass spectra of the different species but also influences the configuration of the mass spectra of the different geographical zones of production.

Poplar and willow demonstrate great potential for the phytoextraction of trace elements (TEs) from soils. In most cases, these species are managed as short-rotation coppice, producing high woody biomass yields, which could provide a valuable contribution toward reducing greenhouse gas emissions in the atmosphere. In the current study, we compared the TE extraction and CO2 sequestration rates in a four-year field trial in Southern Italy of two arboreal species (willow and poplar). The results show that, once established in the study area, willow extracted more Cd and Cu and less Pb than poplar. The two species demonstrated the same average Ni and Zn extraction rates. Greater biomass yields in poplar suggest that this species was able to fix greater amounts of CO2 (28.7 Mg ha−1 yr−1) than willow (24.9 Mg ha−1 yr−1). We argue that the choice of the species to be used in phytoextraction should first be made considering the TE-specific affinity and phytoextraction rates. For TEs whose extraction rates were the same (i.e., Ni and Zn), poplar is to be preferred because of its ability to fix greater amounts of CO2 than willow.

Quince is characterized as a fragrant fruit which, unlike other pomes (apple, pear), is not used for fresh consumption due to its astringency and compactness, but only in its processed form (jams, jelly, distillery products, and nutraceutical compounds). As a consequence, there is little knowledge currently available concerning the characteristics of the fruit, and in particular its aromatic and chemotaxonomic patterns. In this work, carpometric, chemometric and spectrophotometric measurements were performed on quince fruits. VOCs emitted by different tissues or parts of the fruit were studied to describe its aromatic profile. The study was carried out on the fruits of an old, well-known cultivar (‘Gigante di Wranja’, commonly called ‘Wranja’) and a new Tuscan accession. Intact, halved and solely pulp (cubed) samples were evaluated for each individual fruit. Data obtained from VOC analysis through Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS) were evaluated by multivariate statistical analysis. The spectra obtained from the intact fruit samples showed a higher amount of masses corresponding to terpenes or terpenoid compounds, which fundamentally characterize the aroma of this type of fruit; these substances were found to be much less present in the VOCs emitted by the pulp, where high values of masses linked to the maturation processes were instead found.

Virgin olive oils (VOOs) are characterized by peculiar flavors appreciated by the consumers all over the world. Their organoleptic characteristics depend on the aromatic properties of the fruits of the different cultivars, which will originate the final products. VOCs spectra of fifteen certified Italian olive cultivars of the University of Florence Germplasm collection, chosen as their different geographical origin, diffusion, and product purpose, were acquired using a Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS). The VOCs analyses highlighted a great variability among the fifteen cultivars, mostly due to compounds (C6 and C5) deriving from polyunsaturated fatty acids through the LOX pathway. The early identification in the olive fruit of these compounds which are considered among the major contributors to the positive VOOs attributes, would be useful to produce high quality olive oils, and get useful information to individuate the best parents for the genetic improvement.

In this work the emission of volatile organic compounds (VOCs) upon the heating process of an extra virgin olive oil (EVOO) and a high oleic sunflower oil (SFO) was evaluated in real time by spectrometry. Two tests were carried out, in the first VOCs emitted from both kinds of oil were measured at room temperatures (not heated, NH) and at 180°C; in the second test, VOCs emission for selected masses were monitored under increasing temperatures over time: at room temperature not heated oils (NH), 60, 90, 120, 150, and 180°C, respectively. The spectra were acquired using a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-ToF-MS). The total VOCs emission increased at 180°C, determined both by the rise of the amount of compounds present in the NH samples and by the formation of new masses generated by oxidative chemical reaction from triglycerides and fatty acids. From the set of results it is evident that a good control of the temperatures can be useful in reducing the quantities of masses potentially harmful to health in human food.

High-grade gliomas (HGGs) are the most frequently diagnosed primary brain tumors. Even though it has been demonstrated that combined surgical therapy, chemotherapy, and radiotherapy improve survival, HGGs still harbor a very poor prognosis and limited overall survival. Differently from other types of primary neoplasm, HGG manifests also as a neurological disease. According to this, palliative care of HGG patients represents a peculiar challenge for healthcare providers and caregivers since it has to be directed to both general and neurological cancer symptoms. In this way, the end-of-life (EOL) phase of HGG patients appears to be like a journey through medical issues, progressive neurological deterioration, and psychological, social, and affective concerns. EOL is intended as the time prior to death when symptoms increase and antitumoral therapy is no longer effective. In this phase, palliative care is intended as an integrated support aimed to reduce the symptoms burden and improve the Quality Of Life (QOL). Palliative care is represented by medical, physical, psychological, spiritual, and social interventions which are primarily aimed to sustain patients’ functions during the disease time, while maintaining an acceptable quality of life and ensuring a dignified death. Since HGGs represent also a family concern, due to the profound emotional and relational issues that the progression of the disease poses, palliative care may also relieve the distress of the caregivers and increase the satisfaction of patients’ relatives. We present the results of a literature review addressed to enlighten and classify the best medical, psychological, rehabilitative, and social interventions that are addressed both to patients and to their caregivers, which are currently adopted as palliative care during the EOL phase of HGG patients in order to orientate the best medical practice in HGG management.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessively inherited disorder of fatty acid oxidation with a potentially fatal outcome in undiagnosed patients. The introduction of tandem mass spectrometry into newborn screening (NBS) has led to the inclusion of MCADD in NBS in many countries, which has resulted in a significant reduction of morbidity and mortality. We report a child with MCADD presenting neonatally with apnoea and heart arrest. Despite intensive efforts to rescue the child, including reanimation for 90 min, the child died at the second day of life. Autopsy revealed fatty liver and also fat storage in heart muscle, which was suggestive of a fatty acid oxidation defect. However, acylcarnitines determined from stored EDTA blood were not suggestive of MCADD. Nevertheless, a subsequent whole exome sequencing analysis revealed homozygosity for the ACADM gene c.1084A>G/p.Lys362Glu mutation.